1262

PAPER

Neuropathy associated with gluten sensitivity

M Hadjivassiliou, R A Grunewald, R H Kandler, A K Chattopadhyay, J A Jarratt,
D S Sanders, B Sharrack, S B Wharton, G A B Davies-Jones
...............................................................................................................................
J Neurol Neurosurg Psychiatry 2006;77:12621266. doi: 10.1136/jnnp.2006.093534

See end of article for

authors affiliations
.......................
Correspondence to:
M Hadjivassiliou,
Department of Neurology,
The Royal Hallamshire
Hospital, Glossop Road,
Sheffield S10 2JF, UK;
m.hadjivassiliou@sheffield.
ac.uk
Received 23 March 2006
Revised 30 May 2006
Accepted 30 June 2006
Published Online First
11 July 2006
.......................

Objectives: To prospectively study the clinical, neurophysiological and neuropathological characteristics of

axonal neuropathies associated with positive antigliadin antibodies and the prevalence of such
neuropathies in a cohort of patients with sporadic axonal neuropathy.
Methods: Prospective screening (using antigliadin, antiendomysium and tissue transglutaminase
antibodies) of patients with peripheral neuropathy attending a neurology clinic.
Results: 215 patients with axonal neuropathy were screened. 141 patients had symmetrical sensorimotor
neuropathy, 47 had mononeuropathy multiplex, 17 had motor neuropathy and 10 had small-fibre
neuropathy. Despite extensive investigations of the 215 patients, 140 had idiopathic neuropathy. Positive
immunoglobulin (Ig)G with or without IgA antigliadin antibodies was found in 34% (47/140) of the
patients with idiopathic neuropathy. This compares with 12% prevalence of these antibodies in the healthy
controls. The prevalence of coeliac disease as shown by biopsy in the idiopathic group was at least 9% as
compared with 1% in the controls. The clinical features of 100 patients (47 from the prevalence study and
53 referred from elsewhere) with gluten neuropathy included a mean age at onset of 55 (range 24
77) years and a mean duration of neuropathy of 9 (range 133) years. Gluten-sensitive enteropathy was
present in 29% of patients. The human leucocyte antigen types associated with coeliac disease were found
in 80% of patients.
Conclusions: Gluten sensitivity may be aetiologically linked to a substantial number of idiopathic axonal
neuropathies.

luten sensitivity is a state of heightened immunological responsiveness to ingested gluten in genetically

susceptible people.1 It represents a spectrum of diverse
manifestations, one of which is gluten-sensitive enteropathy.
The term coeliac disease should now be restricted to describe
gluten-sensitive enteropathy (triad of villous atrophy, crypt
hyperplasia and increased intraepithelial lymphocytes on
histological examination of small-bowel mucosa). The term
gluten sensitivity describes a spectrum of diseases having in
common an immune response to the ingestion of gluten, but
with diverse manifestations such as an enteropathy (coeliac
disease), dermatopathy (dermatitis herpetiformis) and neurological disorders (eg, gluten ataxia and neuropathy).2 Not
surprisingly, the common aetiological trigger (gluten) means
that these diseases overlap considerably. For example, most
patients with dermatitis herpetiformis also have coeliac
disease, as do a third of patients with gluten ataxia.3
Similarly, 8% of patients with established coeliac disease
develop neurological manifestations.4
A review of all published papers from 1964 to 2000 (single
and multiple case reports) of 83 patients with coeliac disease
who then develop neurological illness shows that the most
common neurological entities encountered were ataxia
(n = 29) and peripheral axonal neuropathy (n = 29).5 We
have previously reported that neurological manifestations
can present even in the absence of an enteropathy. The most
common neurological dysfunction encountered was ataxia
(gluten ataxia) and peripheral axonal neuropathy.6 7 Of 28
patients with axonal peripheral neuropathy, 13 had positive
antigliadin antibodies.6 Most neuropathies encountered were
symmetrical sensorimotor axonal in type. There have since
been additions to the literature on neuropathy and coeliac
disease. One such study showed that among patients with
established coeliac disease on a gluten-free diet, 23% had
evidence of axonal peripheral neuropathy.8 Another study
found that 2.5% of all patients with neuropathy had coeliac

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disease.9 The figure was higher at 8% when patients with

symptoms of neuropathy but normal neurophysiological
assessment were included.9 Given that 1% of the healthy
population has coeliac disease10 with no gastrointestinal
symptoms and as many as 12% may have serological evidence
of gluten sensitivity, the prevalence of gluten sensitivityrelated neuropathy in patients with sporadic axonal neuropathy merits more detailed investigation.
The first aim of this 10-year study was to study
prospectively the prevalence of gluten sensitivity and coeliac
disease (using antigliadin, antiendomysium and transglutaminase antibodies as well as duodenal biopsies) in a large
number of patients with axonal neuropathies. The second
aim was to characterise gluten neuropathy in clinical,
neurophysiological and neuropathological terms.

PATIENTS AND METHODS

Patient selection
All patients with clinical and neurophysiological evidence of
axonal neuropathy were consecutively recruited over a period
of 10 years (19942004) from a general neurology clinic at the
Department of Clinical Neurology, The Royal Hallamshire
Hospital, Sheffield, UK. The consultants running the clinic
(initially GABD-J and then MH) have a particular interest in
patients with chronic idiopathic axonal neuropathy, and such
patients are followed up regularly. Patients with a family
history of neuropathy or positive genetic testing for familial
neuropathies were excluded, as were patients with demyelinating neuropathies such as GuillainBarre syndrome, chronic
inflammatory demyelinating polyneuropathy and multifocal
motor neuropathies with conduction block. Tertiary referrals of
patients with the diagnosis of gluten sensitivity and peripheral
neuropathy referred to the gluten sensitivity/neurology clinic
Abbreviation: HLA, human leucocyte antigen

Neuropathy and gluten sensitivity

by consultant neurologists from Sheffield and other UK

neurology centres were not included in the prevalence part of
the study, but were included for the purpose of defining the
clinical characteristics. For the estimation of prevalence of
antigliadin antibodies and coeliac disease in the healthy
population of the region (similar demographic characteristics),
a separate parallel study (19992001) was conducted and the
results have been published.10 The data from this study were
used for the comparison of the prevalence of antigliadin
antibodies and coeliac disease between healthy controls and
patients with neuropathy.
Investigations of peripheral neuropathy
As part of the screening process for the aetiology of
neuropathy, all patients underwent the following investigations at least once: full-blood count, erythrocyte sedimentation rate, vitamin B12, red cell or serum folate, urea and
electrolytes, liver function tests, thyroid function tests,
random blood sugar, glycosylated haemoglobin (in selected
cases, glucose tolerance test), serum angiotensin-converting
enzyme, immunoglobulins and electrophoresis (with immunofixation), antinuclear antibodies, double-stranded DNA,
extractable nuclear antibodies, antigliadin antibodies (IgG
and IgA), IgA endomysium antibodies, IgA tissue transglutaminase antibodies (the antiendomysium and tissue transglutaminase assays became available half way through the
study, which is why not all patients were tested at baseline),
rheumatoid factor, antinuclear cytoplasmic antibodies and
chest radiograph. Additional investigations were carried out
if clinically indicated, and included borrelia serology,
hepatitis B and C and HIV serology, complement levels,
cryoglobulins, vitamins B1, B6 and E, paraneoplastic antibodies (Hu, Yo and Ri), lead levels, abdominal ultrasound
scan, sural-nerve biopsy, abdominal and chest computed
tomography scan, skeletal survey, bone marrow examination
and positron emission tomography scan.
Additional investigations for patients with
neuropathy and gluten sensitivity
All patients with positive antigliadin antibodies (IgG or IgA)
irrespective of the presence of antiendomysium and tissue
transglutaminase antibodies were offered duodenal biopsy.
Specimens were taken from the distal duodenum using
biopsy forceps, through a conventional forward-viewing
endoscope (Key-Med, Southend, UK). Four biopsy specimens
were taken from the third part of the duodenum. The
presence of gluten-sensitive enteropathy was established by
histological examination for evidence of crypt hyperplasia,
villous atrophy and increase in intraepithelial lymphocyte
count.11
Neurophysiological assessments
Nerve conduction studies and electromyography were carried
out at least once in all patients where clinical evaluation
suggested a diagnosis of peripheral neuropathy. All patients
included in this study had evidence of axonal peripheral
neuropathy on neurophysiological assessments (generalised
sensory or motor peripheral neuropathy, mononeuropathy
multiplex or small-fibre neuropathy). Sensory and motor
nerve conduction studies and EMG were carried out using
standard techniques. Nerve conduction study results were
usually deemed abnormal if values fell outside 99% confidence limits, but allowance was made in interpreting values
with respect to age of the patient. Where nerve conduction
studies were normal and the clinical features were suspicious
of small-fibre involvement, thermal threshold testing was
performed. Thermal threshold results were considered to be
abnormal if they fell outside 99% confidence limits obtained
from age-matched healthy controls.

1263

RESULTS
Prevalence
A total of 215 patients with axonal neuropathy participated
in this study. Of these 141 had symmetrical sensorimotor
axonal neuropathy, 47 had mononeuropathy multiplex, 17
had motor neuropathy and 10 had small-fibre neuropathy.
After investigations, the aetiology of neuropathy was
established in some patients as follows: diabetes mellitus
was the cause of neuropathy in 24 of 215 (11%) patients (7
had type 1 and 17 had type 2 diabetes). In 16 of 215 (7%)
patients, a connective tissue disease or vasculitis was
confirmed to be the aetiological factor. A paraneoplastic
neuropathy was diagnosed in 9 (4%) patients. Low vitamin
B12 was found in 9 (4%) patients. Cases of monoclonal
gammopathy of undetermined significance (n = 5, 2%),
excessive alcohol intake (n = 4, 2%), drug related (n = 3, 2
amiodarone, 1 phenytoin, 1%) and hypothyroidism (with
evidence of improvement of the neuropathy with thyroid
replacement alone; n = 3, 1%) were noted. One patient was
found to have low vitamin B6 and improved with nutritional
support; in another patient the neuropathy was thought to be
related to sarcoidosis (confirmed by biopsy). Thus, a possible
aetiology for the neuropathy was established in 75 patients,
leaving 140 patients with seemingly idiopathic neuropathy.
Positive serology for gluten sensitivity (IgG or IgA antigliadin
antibodies) was found in 47 of 140 (34%) patients with
idiopathic neuropathy. This compared with 12% prevalence of
these antibodies in the control population of Sheffield.10 The
difference in prevalence of antigliadin antibodies between the
two groups was significant (p,0.001 by x2 test). In addition,
7 of 75 (9%) patients with neuropathy of known aetiology
(two with type 1 diabetes and five with low vitamin B12)
were found to have antigliadin antibodies. Of the 47 patients
with gluten sensitivity, 45 underwent duodenal biopsies and
12 (27%) were found to have an enteropathy in keeping with
coeliac disease. Thus, the prevalence of coeliac disease as
determined by biopsy in the idiopathic group was at least 9%
(12/140). This compares with 1% prevalence of coeliac disease
in the controls.9 Table 1 summarises these data.
Clinical characteristics
The clinical and immunological characteristics of the 47
patients with gluten sensitivity and otherwise idiopathic
neuropathy were then combined with those of 53 patients
with gluten sensitivity and neuropathy who had been
referred consecutively to the gluten sensitivity/neurology
clinic from other neurologists from Sheffield and elsewhere
in the UK. All the additional 53 patients were investigated in
a similar manner and other causes of neuropathy were
excluded. Table 2 outlines the clinical features of these 100
patients.
The mean age at onset of the neuropathy was 55 (range
2477) years, with a mean symptom duration of 9 (range 1
33) years. In all, 67 patients had a symmetrical generalised
sensorimotor axonal neuropathy, 17 had mononeuropathy
multiplex, 9 had pure motor neuropathy and 7 had smallfibre neuropathy. Antigliadin IgG antibodies alone were
positive in 57%, antigliadin IgA alone in 16%, and both IgG
and IgA were positive in the remaining 27%. Tissue
transglutaminase antibodies were present in 16 of 44 (36%)
patients and antiendomysium antibodies in 12 of 52 (23%)
patients who underwent these additional tests. Glutensensitive enteropathy was present in 26 of 89 (29%) patients
who underwent duodenal biopsy. The human leucocyte
antigen (HLA) types associated with coeliac disease were
seen in 80% (62% HLA-DQ2, 10% HLA-DQ8, 8% HLA-DR3,
HLA-DR5 or HLA-DR7, without HLA-DQ2 or HLA-DQ8) of
these patients. The remaining had HLA-DQ1. We found no
significant differences in any of the above characteristics

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1264

Hadjivassiliou, Gru newald, Kandler, et al

Table 1 Causes of neuropathy in 215 patients with

chronic axonal neuropathy
Condition

Percentage

Diabetes mellitus (17 type 2, 7 type 1)

Vasculitis or connective tissue disease
Paraneoplastic
Low vitamin B12
MGUS
Alcohol related
Drug related
Hypothyroidism
Low B6
Sarcoidosis

24/215
16/215
9/215
9/215
5/215
4/215
3/215
3/215
1/215
1/215

11
7
4
4
2
2
1
1
0.5
0.5

Total with diagnosis

Idiopathic

75
140

35
65

Positive serology of gluten sensitivity

(whole group)
Duodenal biopsy in keeping with
enteropathy
Positive serology for gluten sensitivity
(idiopathic group)
Duodenal biopsy in keeping with
enteropathy
Positive serology for gluten sensitivity
(diagnosis group)
Duodenal biopsy in keeping with
enteropathy
Positive serology for gluten sensitivity
(healthy population)
Duodenal biopsy in keeping with coeliac
disease

54/215

25

14/215

47/140

34

12/140

7/75

2/75

144/1200

12

12/1200

MGUS, monoclonal gammopathy of undetermined significance.

between the 47 patients from the prevalence study and the 53

patients referred from elsewhere.
Neuropathological findings
Pathological data were available from three patients (suralnerve biopsies in two patients and an autopsy in one).
A sural-nerve biopsy from a 65-year-old man (positive
antigliadin antibodies, normal duodenal biopsy) with clinical
and neurophysiological evidence of sensorimotor axonal
neuropathy showed a focal inflammatory cell infiltrate in
the epineurium and around a small endoneurial blood vessel
in one fascicle (fig 1). The inflammatory cells, which included
plasma cells, were closely related to the vessel wall. Resinembedded thin sections showed a patchy loss of myelinated
fibres and occasional degenerating fibres. Occasional thinly
myelinated fibres were seen, but not demyelinated fibres.
These appearances suggested axonal degeneration secondary
to an inflammatory microvasculopathy. The patients condition is stable while on a gluten-free diet.
Case 2 was a 49-year-old man with asymmetrical sensorimotor axonal neuropathy suggestive of mononeuropathy
multiplex. He had positive antigliadin antibodies, and coeliac
disease was confirmed on duodenal biopsy. He had never been
strict with his gluten-free diet (persistently positive antigliadin
antibodies) and the neuropathy had progressed. He underwent
a fascicular sural-nerve biopsy, containing a single fascicle. This
showed evidence of axonal degeneration, but no evidence of
inflammatory cell infiltration.
Case 3 was a 32-year-old woman who died from a rapidly
progressive neuropathy (symmetrical sensorimotor axonal
neuropathy) and ataxia, whose onset coincided with the
diagnosis of gluten sensitivity. She also had evidence of
enteropathy on biopsy. Autopsy showed inflammatory changes
in both the central and the peripheral nervous systems
(represented by spinal nerve roots). Capillaries in the brain
seemed prominent in some areas, with hypertrophic endothelial cells. These vascular changes were most conspicuous in

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Table 2 Clinical and immunological characteristics of

100 patients with gluten neuropathy
Mean age at onset of neuropathy
Mean duration of disease
Need walking aid
Pain a prominent feature
Sensorimotor axonal neuropathy
Mononeuropathy multiplex
Motor neuropathy
Small-fibre neuropathy
Only antigliadin IgG positive
Only antigliadin IgA positive
Both antigliadin IgG and IgA positive
Tissue transglutaminase antibody positive*
Endomysium antibody positive*
Enteropathy on biopsy
HLA typing in keeping with coeliac disease

55 years (range 2477)

9 years (range 133)
22%
14%
67%
17%
9%
7%
57%
16%
27%
16/44 (36%)
12/52 (23%)
26/89 (29%)
80/100 (80%)

100 patients include 47 patients from the prevalence study and 53

patients with gluten neuropathy referred to the gluten sensitivity/
neurology clinic from elsewhere.
HLA, human leucocyte antigen; Ig, immunoglobulin.
*The antiendomysium and tissue transglutaminase assays became
available halfway through the study, which is why not all patients were
tested at baseline.

white matter, including cerebral, cerebellar and brain stem

white matter. However, similar changes were seen focally in
grey matter areas, including the hippocampus and the inferior
olivary nucleus. The capillary changes were associated with a
vascular and perivascular inflammatory cell infiltrate, predominantly of histiocytes (CD68+) and a lighter population of
small lymphocytes, which were mostly T cells (CD45Ro+).
Occasional fragmenting nuclei, possibly representing apoptotic
bodies, were seen, but there was no vascular necrosis. We
observed no tissue necrosis or microinfarction, and only mild
focal myelin loss. Similar changes were also seen in the spinal
cord. The cerebellum showed loss of Purkinje cells (fig 2A) with
increased Bergmann glia, and there was a mild patchy loss of
neurones in the inferior olivary nucleus. Spinal roots of
peripheral nerve showed inflammatory cell infiltrate of both
lymphocytes and macrophages (fig 2B), some of which were
positive for T cell markers.

DISCUSSION
Demyelinating inflammatory neuropathies have been the
focus of most research on peripheral neuropathies; yet axonal
neuropathies are by far the most common type of neuropathies encountered in everyday neurological practice.12 13
This large prospective study has attempted to identify a
prevalence figure (among patients with sporadic axonal
neuropathy) and clinically characterise gluten sensitivityrelated neuropathy. Data on the prevalence of other causes of
axonal neuropathies are also presented in this study, but are
unlikely to represent the true prevalence of each aetiology in
the general population because of referral bias. For example,
in this study, diabetes accounted for 11% of all the
neuropathies but was found to be the cause of neuropathy
in .50% of patients in another study.12 In the UK, patients
with established and poorly controlled diabetes who have a
neuropathy are less likely to be referred to neurology clinics,
given that the aetiology and treatment of their neuropathy is
apparent. In this study for most patients with non-insulindependent diabetes, the diagnosis of diabetes was made on
the basis of the aetiology of the neuropathy. The figures of
prevalence for the different aetiologies of neuropathy found
in this study reflect more closely what is seen in a longestablished general neurology clinic where patients with
chronic axonal neuropathies are followed up long term.
The principal aim of this study was to investigate the
prevalence of gluten sensitivity among patients with chronic
idiopathic axonal neuropathy as defined by the presence of

Neuropathy and gluten sensitivity

1265

Figure 1 Sural-nerve biopsy specimen from a 65-year-old man with gluten neuropathy, showing a focal inflammatory cell infiltrate in the epineurium
and around a small endoneurial blood vessel (arrow, A). The inflammatory cells were closely related to the vessel wall, but not associated with fibrinoid
necrosis (A,B). Resin-embedded thin sections showed a patchy loss of myelinated fibres and occasional degenerating fibres. Demyelinated fibres were
not seen (C). Teased fibre preparations showed up to 30% of the population of fibres undergoing Wallerian degeneration (arrows, D).

Figure 2 Cerebellum and peripheral nerve tissue obtained at autopsy

from a 32-year-old woman who died from a rapidly progressive
neuropathy and ataxia, the onset of which coincided with the diagnosis
of gluten-sensitive enteropathy. The cerebellum (A) showed a patchy loss
of Purkinje cells (arrow pointing to the only remaining Purkinje cell on
this section) with increased Bergmann glia. Spinal roots of peripheral
nerve (B) showed inflammatory cell infiltrate of both lymphocytes and
macrophages (arrows), some of which were positive for T cell markers.

antigliadin antibodies. To avoid referral bias (in view of our

interest in the neurological manifestations of gluten sensitivity),
we deliberately excluded any patients referred to the gluten
sensitivity/neurology clinic with an established diagnosis of
gluten neuropathy. The prevalence of antigliadin antibody
positivity was 34% in patients with otherwise idiopathic axonal
neuropathy compared with 9% in patients with established cause
of neuropathy and 12% in controls from the same region.10 The
prevalence of coeliac disease among these patients was found to
be at least 9% and compares with 1% in the controls from the
same region.10 It is also possible that in those seven patients with
neuropathy of known aetiology (two patients with type 1
diabetes and five patients with low vitamin B12) who also had
antigliadin antibodies, the aetiology of the neuropathy could be
linked to gluten sensitivity rather than to diabetes or low vitamin
B12. We, however, found no correlation between vitamin B12
deficiency and the presence of enteropathy.
A previous controlled study has shown that as many as
23% of patients with established coeliac disease on a glutenfree diet showed axonal neuropathy on neurophysiological
testing.8 Given that at least 1% of the healthy population in
European countries and the US has coeliac disease and up to
12% has serological evidence suggestive of gluten sensitivity,
such sensitivity may well prove to be a common aetiological
link to chronic idiopathic axonal neuropathy.
Some clinicians choose to distinguish between those
patients with gluten sensitivity who have an enteropathy
(coeliac disease) and those without an enteropathy but with
positive serological markers for gluten sensitivity. The
rationale for this is not clear, as gluten sensitivity represents
a spectrum ranging from antibody-positive but normal smallbowel mucosa (often referred to as potential coeliac disease
or Marsh stage 01) to the presence of the classic small lesions
on a biopsy sample, which define coeliac disease. The range
of changes seen on examination of the small-bowel mucosa,
which may relate to gluten load, has been documented in

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1266

detail and is now known as the Marsh classification.14 Thus,

in the case of our patients with peripheral neuropathy
associated with gluten sensitivity, there is nothing on clinical,
genetic or immunological grounds to distinguish between
patients with or without enteropathy. Extraintestinal manifestations can be the presenting feature of this disease (eg,
dermatitis herpetiformis, gluten ataxia), and such manifestations can be successfully treated with a gluten-free diet even
in the absence of enteropathy.15 We therefore propose the
term gluten neuropathy to describe this entity. Such a term
encompasses patients with positive antigliadin antibodies
with or without the bowel being affected (coeliac disease)
and in the absence of an alternative aetiology for the
neuropathy. The HLA type may offer additional diagnostic
value, given that 80% of these patients have HLA-DQ2 or
HLA-DQ8. Tissue transglutaminase and antiendomysium
antibodies are good markers for the presence of an enteropathy (coeliac disease) but lack sensitivity when the bowel
mucosa is normal and the disease presents with extraintestinal manifestations. Some patients reported in this study
probably had a neuropathy that was coincidentally rather
than aetiologically linked with the presence of circulating
antigliadin antibodies. This is inevitable given that as yet
there are no specific serological markers for the neurological
spectrum of gluten sensitivity. Antigliadin antibodies currently remain the most sensitive markers of the whole
spectrum of gluten sensitivity. The prospect of an additional
marker seems imminent after the recent discovery that in
vivo IgA deposits against tissue transglutaminase type 2 in
the small-bowel biopsy specimens of patients with diverse
manifestations within the spectrum of gluten sensitivity are
detected even in the absence of enteropathy. Such deposits
have also been found in extraintestinal tissue, such as vessels
in the cerebellum in patients with gluten ataxia. This marker
seems to be highly specific for the whole spectrum of gluten
sensitivity, as it was not found to be present in healthy and
disease control subjects.16
The pathophysiology of gluten neuropathy remains unclear.
Nutrient and vitamin deficiencies are unlikely to play a part,
given that most of these patients have a normal nutritional
status and no enteropathy. The mechanism is more likely to be
immunological along the same lines as gluten ataxia.17 The
pathology is that of an inflammatory process as outlined in this
study and reported previously.7 This process can clearly affect
peripheral nerves as well as the central nervous system.1820
More often than not, however, the biopsy findings are those of
axonal degeneration without evidence of inflammation.
Patients with gluten sensitivity may rarely present with a
rapidly progressive neuropathy, often associated with involvement of the central nervous system, as described for case 3 in
Neuropathological findings. Such cases have previously been
described by Cooke and Thomas-Smith.20 On the basis of this
study and the review of published case reports, the most
common neuropathy encountered in the context of gluten
sensitivity is that of a chronic slowly progressive symmetrical
sensorimotor axonal distally predominant peripheral neuropathy. Further evidence in support of gluten neuropathy being
immune mediated comes from a report on the presence of
antiganglioside antibodies in patients with coeliac disease and
neuropathy.21
Why the same disease (gluten sensitivity) results in both
symmetrical and at times asymmetrical neuropathy (mononeuropathy multiplex), or even pure motor or sensory
neuropathy remains unclear. This diverse pattern of peripheral
nerve involvement is also seen in other diseases such as
diabetes mellitus or neuropathy associated with connective
tissue diseases. In one of our patients with gluten sensitivity,
we observed progression of the motor neuropathy to involvement of sensory fibres with continuous exposure to gluten.22 It

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Hadjivassiliou, Gru newald, Kandler, et al

is yet unclear whether the aetiology of the mononeuropathy

multiplex seen in some of these patients with gluten sensitivity
is mediated through a low-grade vasculitic process.
We conclude that serological evidence of gluten sensitivity
is commonly found in chronic idiopathic axonal neuropathies
and may well be aetiologically linked. The effect of a glutenfree diet on the neuropathy should confirm whether or not
this is another manifestation of gluten sensitivity similar to
gluten ataxia, dermatitis herpediformis and gluten-sensitive
enteropathy.
.....................

Authors affiliations

M Hadjivassiliou, R A Grunewald, B Sharrack, G A B Davies-Jones,

Department of Neurology, The Royal Hallamshire Hospital, Sheffield, UK
R H Kandler, A K Chattopadhyay, J A Jarratt, Department of
Neurophysiology, The Royal Hallamshire Hospital
S B Wharton, Department of Neuropathology, The Royal Hallamshire
Hospital
D S Sanders, Department of Gastroenterology, The Royal Hallamshire
Hospital
Competing interests: None.
Ethical approval: The South Sheffield Research Ethics Committee
approved the study protocol, and all patients provided written informed
consent.

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